BACKGROUND: Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. RESULTS: We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. CONCLUSION: This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.

mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer

LANZA, Giovanni;FERRACIN, Manuela;GAFA', Roberta;VERONESE, Angelo;SPIZZO, Riccardo;CROCE, Carlo Maria;NEGRINI, Massimo
2007

Abstract

BACKGROUND: Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. RESULTS: We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. CONCLUSION: This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.
2007
Lanza, Giovanni; Ferracin, Manuela; Gafa', Roberta; Veronese, Angelo; Spizzo, Riccardo; Pichiorri, F; Liu, C. G.; Calin, G. A.; Croce, Carlo Maria; Negrini, Massimo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/471279
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